Delivery vehicle for silver ions

ABSTRACT

A delivery vehicle for a silver ion source such as silver nitrate and the like, suitable for use in the treatment of menorrhagia, comprises a plurality of physiologically inert beads bearing a tissue cauterizing amount of a silver ion source. Preferably the beads are made of a physiologically inert polymer, ceramic or stainless steel. The silver ion source preferably is silver nitrate and can be substantially pure silver nitrate, or can comprise silver nitrate in combination with a physiologically tolerable binder or a diluent. Suitable binders include physiologically tolerable synthetic polymeric binders, polysaccharide binders, and the like. Diluents can include other salt materials such as potassium nitrate. The beads are useful in treating menorrhagia of a mammalian uterus. The beads can be delivered to the uterus via a catheter, and are distributed throughout the uterine cavity by uterine massage or like expedient. Silver ions are delivered to the endometrium and cause necrosis of the endometrial tissue. The silver ions remaining within the uterine cavity can then be neutralized with a sodium chloride solution delivered to the uterus e.g., by catheter, and the beads recovered from the uterus.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims benefit of U.S. Provisional Patent ApplicationNo. 60/463,255, filed Apr. 16, 2003.

FIELD OF THE INVENTION

This invention relates generally to vehicles for delivering tissuenecrosing agents. More specifically, the invention relates to inertbeads having a silver ion releasing compound such as silver nitratedeposited thereon, and suitable for delivering a tissue cauterizingamount of silver ions to the endometrium of a mammalian uterus for thetreatment of menorrhagia.

BACKGROUND OF THE INVENTION

Apparatus and methods for necrosing of the endometrium of a mammalianuterus, useful in treating excessive bleeding (menorrhagia)sterilization procedures, and cancer treatments, are known in the art.Thermal and cryogenic treatments have been utilized in such necrosingtechniques and typically involve either the direct or indirectapplication of heat or cold to the tissue to be treated.

In addition to thermal and cryogenic treatments, methods involvingapplication of caustic chemicals within the human body to treatmenorrhagia, achieve sterilization and treat cancers also are known. Theuse of caustic chemicals as locally destructive agents has beenattempted but has been limited by concerns about safety and control ofthe delivery of various agents as well as other shortcomings due to themethods of application, e.g., blind placement of a particular solidchemical. For example, as described by Babcock, W., ChemicalHysterectomy, Jnl. Obstet. & Gyn., Vol. 7, p. 693 (1924), application ofgauze strips soaked in a saturated solution of zinc chloride to theuterine walls has reportedly been used to induce amenorrhea, to causesterility, and to treat tumors. However this procedure has severaldisadvantages. The application of the gauze strips is a blind procedure,however. The zinc chloride soaked gauze is packed in the uterus untilthe practitioner feels the cavity is full. The strips are left in placefor a predetermined length of time and then removed. Delivery to andremoval from the uterine cavity of the caustic gauze strips necessarilyentails substantial risk of infection and of contacting the vaginalwalls wherein the caustic could damage the vaginal and other tissue thatare not the target of the treatment. Accordingly, successful use of thismethodology requires substantial skill and experience, limiting theavailability of the procedure to women with access to highly trainedmedical personnel.

Use of caustic agents such as silver nitrate, zinc chloride and coppersulfate has been studied for use in chemical sterilization by chemicallycauterizing the fallopian tubes. However, as discussed by Richart, R.,Female Transcervical Sterilization, Chapter 3, Harper & Row (1983), evenwhen massive tubal necrosis was achieved with the application of silvernitrate, a significant proportion of fallopian tubes remained open. Whencompositions for the sustained release of the caustic agents wereemployed it was found that control over the release of the causticagents was insufficient to avoid unacceptable side effects.Additionally, use of strong caustic agents such as acids and alkalieswould require the concomitant use of equally strong neutralizing agentswhose use is also laden with risk. Use of such agents also puts thepractitioner in the difficult position of titrating the neutralizationof the caustic agent in the patient's uterus and Fallopian tubes.

Neuwirth describes a particularly effective method for treatingmenorrhagia, which involves administering a silver nitrate-containingpaste to the uterine cavity and distributing the paste therein. See,e.g., U.S. Pat. Nos. 6,197,351; 6,187,346; 6,165,492; and 5,891,457; therelevant disclosures of which are incorporated herein by reference. Thesilver nitrate causes necrosis of the endometrium, which in turn stopsexcess uterine bleeding associated with menorrhagia. After treatment,the caustic silver nitrate is effectively neutralized by administering asolution of sodium chloride, usually physiologic saline, to the uterinecavity. Sodium chloride reacts with the silver nitrate to form insoluble(non-caustic) silver chloride. The silver chloride is then flushed outof the uterus along with any loose necrosed tissued present in theuterus.

Delivery of silver nitrate as a paste, as described by Neuwirth,requires some degree of care to ensure that the paste does not come intoprolonged contact with tissues that are not in need of cauterizationsuch as the Fallopian tubes. There exists, therefore, a need forimproved vehicles for a more precise delivery of silver nitrate to theuterine cavity to implement chemical cauterization of the endometrium.The present invention provides such improved delivery vehicles.

SUMMARY OF THE INVENTION

A delivery vehicle for a silver ion releasing compound such as silvernitrate suitable for tissue necrosis, e.g., for use in the treatment ofmenorrhagia, comprises a plurality of physiologically inert beadsbearing a tissue necrosing amount of a solid silver ion releasingcomposition. The beads can be composed of any physiologically inertmaterial such as a polymer, a ceramic or stainless steel. The solidsilver ion releasing composition can be a water-soluble inorganic silversalt, a water-soluble organic silver salt, and the like water-solubleoxidizing agent. A preferred water soluble inorganic silver salt issilver nitrate, which can be administered as substantially pure silvernitrate, as silver nitrate in combination with a physiologicallytolerable binder or a diluent. A preferred water-soluble organic silversalt is silver acetate, and the like, alone or in combination with aphysiologically tolerable binder or diluent. Suitable binders includephysiologically tolerable synthetic polymeric binders, polysaccharidebinders, and the like. Diluents can include other water soluble saltssuch as potassium nitrate, and the like.

The beads are preferably substantially spherical in shape and have anaverage diameter in the range of about 1 to about 6 millimeters, morepreferably about 2 to about 4 millimeters. Preferably the beads aresubstantially uniform in size.

Preferably each bead carries a composition containing at least about 20milligrams, more preferably about 50 milligrams to about 150 milligramsof a silver ion releasing compound such as silver nitrate, silveracetate, and the like, per bead.

The beads carrying a silver ion releasing composition are useful intreating menorrhagia of a mammalian uterus. The beads are delivered tothe uterus via a catheter, and are distributed throughout the uterinecavity by uterine massage or like manipulation. Silver ions aredelivered to the endometrium and cause necrosis of the endometrialtissue as well as some of the myometrium. The silver ions remainingwithin the uterine cavity can thereafter be neutralized, usually with asodium chloride solution delivered to the uterus by catheter. Thereafterthe beads are recovered from the uterus, for example, by suction, byflushing, by mechanical removal, or the like expedient.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, FIG. 1 is a cross-sectional view of a bead having asilver nitrate-containing composition coated on the exterior surface ofthe bead;

FIG. 2 is a cross-sectional view of a porous bead having a silvernitrate-containing composition deposited within the pores of the bead;

FIG. 3 is a photograph of a section of beef muscle tissue showing thepositioning of two silver nitrate-bearing beads thereon and asurrounding region of necrosis;

FIG. 4 is a photograph of the same section of beef muscle tissue as thatshown in FIG. 3 but after neutralization with physiologic saline afterthe beads have been removed;

FIG. 5 is a section of the beef muscle tissue taken along plane 5-5 inFIG. 4; and

FIG. 6 is a section of the beef muscle tissue taken along plane 6-6 inFIG. 4.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

As used herein, the term “necrosis” and grammatical variations thereofmeans death of cells in a tissue. The term “chemical necrosis” andgrammatical variations thereof means necrosis resulting from contactwith a caustic chemical agent. The terms “physiologically inert” and“physiologically tolerable” as used herein and in the appended claims inreferences to materials or chemical components of the delivery vehiclesof the present invention mean that the material or chemical componentdoes not produce an adverse physiological reaction to the patient whenpresent in the uterine cavity of the patient. Adverse physiologicalreactions include, for example, allergic and other systemic reactions,local inflammation not attributable to the silver nitrate, and the like.

The present invention provides a vehicle suitable for delivering asilver ion source such as silver nitrate and the like to the uterinecavity of a patient suffering from menorrhagia to chemically necrose theendometrium. The delivery vehicle comprises a plurality ofphysiologically inert beads bearing a solid silver ion source. The solidsilver ion source adheres firmly to the beads, but the beads readilyrelease a silver ion bearing composition when the beads come intocontact with the moist endometrium of the uterus. The solid silver ionsource can be coated on the external surface of a bead, or can bepresent at least partially within a porous bead.

Preferably the beads are substantially spherical in shape and have anaverage diameter in the range of about 1 to about 6 millimeters, morepreferably about 2 to about 4 millimeters.

The beads can be made of any physiologically inert material which canmeet governmental regulatory requirements, such as United States Foodand Drug Administration requirements for medical devices received withinthe uterine cavity. The bead can be composed of a physiologically inertpolymer such as polystyrene, polyethylene, polypropylene, nylon,polyethyleneterephthalate (PET), polyurethane, ethylene/vinyl acetatecopolymers, and the like. Alternatively the beads can be made of aphysiologically inert ceramic or of stainless steel. The beads can beperforated, spongiform, porous, or non-porous. Porous beads can bepolymeric foam beads, such as polypropylene foam or polyethylene foambeads, or can be beads having machined pores or perforations, moldedpores, and the like. Preferably the beads are nylon, polystyrene orpolypropylene beads, more preferably having a specific gravity of lessthan 1 so that the beads can be readily removed from the uterine cavityafter treatment by flushing with a saline solution or like expedient.Perforations or grooves in the beads, when present, can increase theloading of a silver ion releasing compound, such as silver nitrate,carried by the beads. For example, the beads can include one or morethrough perforations which can be filled with a silver ion releasingcomposition. Alternatively, the beads can have cavities or pits in thesurface of the beads to hold additional silver ion source therein.Reticulated polyurethane beads are also suitable.

The silver ion delivery vehicles of the present invention can bemanufactured by a variety of methods known in the art. For example, thebeads can be coated with a molten silver nitrate composition, such assubstantially pure silver nitrate, or a mixture of silver nitrate and upto about 25 weight percent of a diluent such as potassium nitrate,preferably no more than about 20 weight percent potassium nitrate, morepreferably no more than about 5 percent by weight potassium nitrate. Themolten silver nitrate composition can be deposited on the beads byspraying, for example, by spraying a molten silver nitrate compositiononto a fluidized bed of beads. The beads also can be coated by combiningthe beads with a molten silver nitrate composition in a rotating kiln, apin blender, and the like. Pure silver nitrate melts at a temperature ofabout 212° C. When a molten silver nitrate composition is deposited on abead, preferably the bead has a softening temperature or a melting pointabove the melting point of the silver nitrate composition.

Alternatively, an aqueous composition containing a silver ion sourcesuch as a water-soluble inorganic silver salt, e.g., silver nitrate,silver sulfate, silver perchlorate, silver permanganate, and the like,or a water soluble organic silver salt, e.g., silver acetate, silverlactate monohydrate, and the like, together with a binder can bedeposited on the beads and dried to provide silver ion delivery vehiclesof the present invention. The aqueous composition can be a paste or afluid containing a thickening binder (e.g., a dextran and the like),such as are described in U.S. Pat. No. 6,197,351 to Neuwirth, therelevant disclosures of which are incorporated herein by reference.Other suitable binders include any physiologically tolerable binder,such as synthetic polymeric binders and thickeners (e.g., poloxamerpolymers, carbomer polymers, polyvinylpyrrolidone, and the like),gelatin, hardened gelatin, polysaccharides (e.g., dextrans,microcrystalline cellulose, methylcellulose, xanthan gum, guar, gum, andthe like), and like thickening and binding agents, so long as they areof a grade suitable for use in intrauterine preparations.Pharmaceutically acceptable binders, carriers, diluents, disintegrants,and the like are described in Remington's Pharmaceutical Sciences, 14thEd., Mack Publishing Co., pp. 1650-1653 (1970), the relevant disclosuresof which are incorporated herein by reference to the extent pertinent.

In one preferred coating method, the silver nitrate-containingcomposition can be an aqueous composition comprising silver nitrate anda polymeric binder such as polyvinylpyrrolidone, and the like. Thecomposition can be applied to the beads in any suitable manner.Preferably, the composition is applied as a uniform coating having arelatively smooth surface structure and a relatively constant thickness.For example, the composition may be applied to the beads by utilizing apneumatic spray gun, by dipping, and the like expedients. Ideally,spraying is continuous, with substantially concurrent drying so that thebeads do not become too moist (overly wet) and stick together. Thefreshly sprayed silver nitrate coating is dried as quickly as possibleto avoid agglomeration of the beads. Other suitable methods include theuse of fluidized-bed processes to coat the beads with a silver nitratecomposition. Modified coating drums (e.g., cylindrical horizontallyrotating units with a perforated wall) are also suitable for coating thebeads with silver nitrate.

In another preferred embodiment, solid silver nitrate, as a powder or asfine crystals, can be added as a filler to a polymer melt, optionallywith a blowing agent, during the bead-making process. Beads of silvernitrate filled polymer can then be extruded to form a silver nitratedelivery vehicle comprising a porous bead with silver nitrate dispersedtherein. Preferably the bead is water swellable or water permeable, sothat silver nitrate in the interior of the bead can be released when thebeads are in contact with the endometrium in the uterus. Alternatively,an aqueous silver nitrate solution can be imbibed into a preformed,porous, water swellable or water permeable polymer bead.

FIG. 1 is a cross-sectional view of a silver nitrate delivery vehicle10, comprising a polymeric bead 12, such as a polypropylene orpolystyrene bead, having a layer 14 of silver nitrate dispersed inpolyvinylpyrrolidone deposited on the surface of bead 12. FIG. 2 is across-sectional view of a silver nitrate delivery vehicle 20 comprisinga porous polymeric bead 22 having silver nitrate 24 within the pores ofbead 22.

Porous beads preferably have an open cell structure and are composed ofa hydrophilic polymer which is water permeable such as nylon orpolyurethane, for example, or have surfaces that are hydrophilic.

Blowing agents that can be used to form porous polymeric materials arewell known in the art. Suitable blowing agents and methods ofmanufacturing foamed polymeric materials are described in Frados,Plastics Engineering Handbook of the Society of Plastics Industry, Inc.,Chapter 20, Van Nostrand Reinhold Co., New York, pp. 499-599 (1976).Suitable blowing agents include, for example, chemical blowing agentssuch as azobisisobutyronitrile, azodicarbonamide, and the like; andgases such as carbon dioxide, nitrogen, and the like.

The plurality of beads delivered to the uterus includes a sufficientquantity of silver ions to produce the level of endometrial necrosisdesired by the clinician performing the treatment. The released silverions (Ag⁺) react in the cells with moieties such as proteins, sulfides,chlorides, and the like that are vital to cell metabolism and thusinitiate necrosis. Preferably a sufficient number of beads isadministered to the uterine cavity to provide a total quantity of silverions in the range of about 25 mg/cm² to about 150 mg/cm² of endometrium,preferably about 50 mg/cm² to about 100 mg/cm² of endometrium.

For a human uterine cavity of normal size, preferably about 15 to about25 silver ion bearing beads having an outside diameter of about 2 toabout 4 millimeters are introduced at one time. More preferably about 20such beads are introduced into the uterine cavity at a time.

In the case of silver nitrate, preferably each bead can release anamount of silver nitrate in the range of about 20 to about 150milligrams, more preferably about 50 to about 150 milligrams.

Another aspect of the present invention is a method of treatingmenorrhagia comprising the steps of administering to the uterine cavityof a patient suffering from menorrhagia a plurality of physiologicallyinert beads bearing a tissue cauterizing amount of a solid silver ionsource such as silver nitrate and the like; massaging the uterus todistribute the beads therein; maintaining the beads in contact with theendometrial lining of the uterus for a time period sufficient to necrosethe endometrial tissue; flushing the uterine cavity with an aqueoussaline solution to neutralize the silver ions present in the uterinecavity; and recovering the beads from the patient's uterus in anyconvenient manner.

The present invention is illustrated by the following examples.

EXAMPLE 1 Preparation of AgNO₃ Bearing Beads

A. Preparation of Coating Solutions

Coating Solution A was prepared by dissolving about 1 gram of silvernitrate in about 4 milliliters of water and adding thereto a solution ofabout 0.4 grams of polyvinylpyrrolidone (K-120) in about 4 millilitersof water.

Coating Solution B was prepared by adding about 4 milliliters of 70%denatured ethanol to about 8 milliliters of Coating Solution A.

B. Coating of Beads

(i) Polypropylene beads having a diameter of about 3 millimeters andperforated polystyrene beads having a diameter of about 5 millimeterswere soaked in Coating Solution A for about 2 minutes, removed from thecoating solution, and were dried at ambient room temperature for about30 minutes. The perforated polystyrene beads had single, substantiallycylindrical through perforation having a diameter of about 1 millimeterin each bead.

(ii) Polypropylene and polystyrene beads as described in (i) above weresoaked in Coating Solution B for about 2 minutes, removed from thecoating solution, and were dried at ambient room temperature for about30 minutes.

(iii) The surfaces of polypropylene and perforated polystyrene beads asdescribed in (i) above were roughened and the beads were then coatedwith Coating Solution A as described in (i) above. The surface of eachbead was roughened by rolling the bead under a file using a circularoscillating motion (about 25 oscillations) followed rolling the beadunder an emery board using a circular oscillating motion (about 50oscillations).

(iv) Surface roughened polypropylene and polystyrene beads as describedin (iii) above were soaked in Coating Solution B for about 2 minutes,removed from the Coating Solution, and were dried at ambient temperaturefor about 10 minutes. The beads were then returned to the CoatingSolution B for about 1 minute, removed, and dried for an additional 10minutes. Finally, the twice-coated beads were returned to CoatingSolution B for about 1 minute, removed from the solution, and were driedat ambient room temperature for about 30 minutes.

EXAMPLE 2 Tissue Necrosis With AgNO₃ Bearing Beads

Silver nitrate bearing beads prepared in Example 1 were placed on thesurface of beef muscle tissue (fillet mignon). Beads without a silvernitrate coating were also placed on the tissue as negative controls, aswas a crystal of pure silver nitrate (about 1 mm diameter by 3 mmlength; as a positive control).

The surface of the tissue under each bead was observed at about 5 minuteintervals for a total of about 15 to about 20 minutes. The degree ofnecrosis of the tissue under each bead was noted at each observation.The degree of necrosis was rated as follows:

slight visible pitting of the tissue surface (+); moderate pitting oftissue surface with slight blackening of the tissue (++); significantpitting with moderate blackening of the tissue (+++); severe pittingwith complete blackening of the tissue (++++); and severe pitting withcomplete blackening of the tissue, spreading beyond the point of contact(+++++).

TABLE 1 Tissue Necrosis Time (Minutes) Bead Batch 5 10 15 20 AgNO₃Crystal +++ ++++ +++++ N/A PP Control — — — --- PS Control — — — ---Smooth Surface PP (i) + N/A ++ ++^(a) PS (i) + N/A ++ ++^(b) PP (ii) +++ +++ N/A^(c) PS (ii) ++ +++ ++++ N/A^(a) Rough Surface PP (iii) ++ +++++++ N/A^(a) PS (iii) ++ +++ ++++ N/A^(a) PP (iv) + + ++ N/A^(a) PS(iv) + ++ +++ N/A^(a) — = no observed necrosis; PP = polypropylene; PS =polystyrene ^(a)= bead penetrated the tissue to a depth of about ½ thediameter of the bead ^(b)= bead penetrated the tissue to a depth ofabout ¼ of the diameter of the bead ^(c)= bead penetrated the tissue toa depth of about ⅓the diameter of the bead N/A = not ascertained

The degree of tissue necrosis observed for each bead type is recorded inTable 1. The data in Table 1 indicate that the silver nitrate coatedbeads as described herein provide an effective vehicle for delivering atissue necrosing amount of silver nitrate to mammalian tissue.

EXAMPLE 3 Tissue Necrosis With Acylonitrile-Butadiene-Styrene Beads

Two acrylonitrile-butadiene-styrene (ABS) beads (4 mm outside diameter)coated with a mixture of silver nitrate and potassium nitrate (50 mgtotal; AgNO₃:KNO₃ weight ratio 95:5) were inserted into beef muscletissue (filet mignon). The beef muscle tissue was pre-heated to 37° C.in a warm water bath and then exposed to the coated beads for 20 minuteswhile at 37° C. and ambient pressure. The beads were held in directcontact with the beef muscle tissue during this time period so as tosimulate the conditions in the uterine cavity. The two coated beads inthe been muscle tissue were spaced about 10 millimeters apart.

After 20 minutes the beef muscle tissue was sliced open so as to revealtissue that had been in contact with the AgNO₃ bearing surface of theABS beads. The degree of achieved necrosis is shown in FIG. 3. Theradius of necrosis (light gray region) around each bead was measured tobe about 10 mm, and extended over the entire distance between the twobeads. Also noted were some white regions believed to be silver chlorideprecipitate.

The so treated beef muscle tissue specimen was then washed with analiquot of physiologic saline (10 ml; 0.9 w/v % of sodium chloride inone liter of water) to neutralize silver ions (Ag⁺) present, and toprecipitate as silver chloride (AgCl). Appearance of the specimen afterneutralization is shown in FIG. 4.

The light gray regions seen in FIG. 3 were observed to be covered with awhite precipitate. This indicated that some of the silver ions releasedfrom the beads had not as yet diffused into the beef muscle tissue.

To evaluate further the extent of necrosis by the two silver nitratebearing beads, the specimen was sectioned along plane 5-5 in FIG. 4,i.e., across the midline of the indentations left by the beads, and thenfolded back unto itself. The appearance of this section is shown in FIG.5. The depth of necrosis was measured to be about 3 mm. The necrosedportion was observed to be harder than the surrounding portions withoutnecrosis, indicating a possible tissue fixation in addition to thetissue oxidation by the silver nitrate.

Thereafter, the specimen shown in FIG. 5 was sectioned at a right angleto that shown in FIG. 5 and as indicated in FIG. 4 by plane 6-6. Theappearance of this particular section is shown in FIG. 6. The necrosedregion is substantially the same as that seen in FIG. 5 and indicatesthat silver nitrate had been diffusing into the tissue from the coatedbeads at substantially the same rate and to substantially the same deptharound the bead.

The foregoing description is to be taken as illustrative, but notlimiting. Still other variants within the spirit and scope of thepresent invention, including other uses for silver nitrate bearingbeads, will readily present themselves to those skilled in the art.

1. A delivery vehicle for silver nitrate for use in the treatment of menorrhagia and comprising a plurality of separate, pbysiologically inert beads bearing a tissue necrosing amount of silver nitrate coated on the surface of each bead, the beads having an average diameter in the range of about 1 to about 6 millimeters.
 2. A delivery vehicle for silver nitrate for use in the treatment of menorrhagia and comprising a plurality of separate, physiologically inert beads bearing a tissue necrosing amount of a silver nitrate coating on the surface of each bead, the beads having an average diameter in the range of about 1 to about 6 millimeters and the silver nitrate being present as a composition that comprises at least 75 percent by weight silver nitrate.
 3. The delivery vehicle of claim 2 wherein the silver nitrate is present as a composition that comprises at least 95 percent by weight silver nitrate.
 4. The delivery vehicle of claim 3 wherein the silver nitrate is present as a composition that comprises up to about 5 percent by weight potassium nitrate.
 5. The delivery vehicle of claim 2 wherein the silver nitrate composition is present in a physiologically tolerable binding matrix.
 6. The delivery vehicle of claim 5 wherein binding matrix is selected from the group consisting of a synthetic polymeric binder, a gelatin binder, a polysaccharide binder, and a combination thereof.
 7. The delivery vehicle of claim 6 wherein the binding matrix is a polysaccharide.
 8. The delivery vehicle of claim 6 wherein the binding matrix is a synthetic polymer.
 9. The delivery vehicle of claim 8 wherein the synthetic polymer is polyvinylpyrrolidone.
 10. The delivery vehicle of claim 2 wherein the physiologically inert beads are porous.
 11. The delivery vehicle of claim 2 wherein the beads are polymeric beads.
 12. The delivery vehicle of claim 2 wherein the beads are polypropylene beads.
 13. The delivery vehicle of claim 2 wherein the beads are polystyrene beads.
 14. A delivery vehicle for a silver ion releasing compound for use in the treatment of menorrhagia and comprising a plurality of separate, physiologically inert beads bearing about 20 to about 150 milligrams of silver nitrate per bead coated on the surface of each bead, the beads having an average diameter in the range of about 1 to about 6 millimeters.
 15. The delivery vehicle of claim 14 wherein the beads bear about 50 to about 150 milligrams of silver nitrate per bead.
 16. A delivery vehicle for silver nitrate for use in the treatment of menorrhagia and comprising a plurality of separate, physiologically inert beads bearing a tissue necrosing amount of silver nitrate composition in a physiologically tolerable polysaccharide binding matrix and wherein the polysaccharide is a dextran. 